(F1222) FEASIBILITY OF USING STEM-CELL DERIVED HUMAN TROPHOBLASTS FOR MASS PROPAGATION OF LIVE ATTENUATED VACCINE STRAINS OF SARS-CoV-2 AND OTHER VIRUSES

Abstract: Existing vaccines for SARS-CoV-2 are less satisfactory in providing mucosal
immunity to block viral transmission. An ideal vaccine should elicit long-lasting and
robust protection in the mucosa, which is crucial to prevent reinfection. We have
previously constructed a dually inactivated SARS-CoV-2 named d16i3a, which is
severely attenuated in vitro and in vivo. The 2'-O methyltransferase activity of NSP16
in d16i3a has been inactivated and the ORF3a accessory gene has also been disrupted. The robustness of d16i3a in inducing mucosal and cross-variant protection in animal
models indicates its potential to be used as a booster vaccine against SARS-CoV-2. In
addition, we have also substituted the ancestral viral spike with that derived from the
Omicron XBB.1.16 variant so that optimal protection against emerging variants can
be achieved. Since it is severely attenuated, mass production of d16i3a requires
special cell lines that have been optimized for viral propagation. Our previous work
has shown that human early syncytiotrophoblasts derived from trophoblast stem cells
are highly susceptible to SARS-CoV-2 infection. However, the susceptibility varies
among derivatives of the trophoblast stem cells and its differentiation stages. In this
study we optimized the derivation of SARS-CoV-2-susceptible human early
syncytiotrophoblasts from trophoblast stem cells. The cells were further engineered to
enhance virion production of recombinant SARS-CoV-2 viruses. Their potential for
mass production of other viruses including influenza A virus was also assessed. Our
findings suggest that stem cell-derived human trophoblasts might be developed as a
tool for mass production of live attenuated vaccine strains of SARS-CoV-2 and other
emerging viral pathogens.

Funding Source: Hong Kong Health and Medical Research Fund grant COVID190114
Hong Kong Research Grant Council T11-709/21-N
Innovation and Technology Commission grant Mainland-Hong Kong Joint Funding Scheme MHP/128/22

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